Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids.
Stem Cell Reports
; 16(3): 437-445, 2021 03 09.
Article
in English
| MEDLINE | ID: covidwho-1084274
ABSTRACT
COVID-19 is a transmissible respiratory disease caused by a novel coronavirus, SARS-CoV-2, and has become a global health emergency. There is an urgent need for robust and practical in vitro model systems to investigate viral pathogenesis. Here, we generated human induced pluripotent stem cell (iPSC)-derived lung organoids (LORGs), cerebral organoids (CORGs), neural progenitor cells (NPCs), neurons, and astrocytes. LORGs containing epithelial cells, alveolar types 1 and 2, highly express ACE2 and TMPRSS2 and are permissive to SARS-CoV-2 infection. SARS-CoV-2 infection induces interferons, cytokines, and chemokines and activates critical inflammasome pathway genes. Spike protein inhibitor, EK1 peptide, and TMPRSS2 inhibitors (camostat/nafamostat) block viral entry in LORGs. Conversely, CORGs, NPCs, astrocytes, and neurons express low levels of ACE2 and TMPRSS2 and correspondingly are not highly permissive to SARS-CoV-2 infection. Infection in neuronal cells activates TLR3/7, OAS2, complement system, and apoptotic genes. These findings will aid in understanding COVID-19 pathogenesis and facilitate drug discovery.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Brain
/
Organoids
/
Induced Pluripotent Stem Cells
/
Neural Stem Cells
/
SARS-CoV-2
/
COVID-19
/
Lung
Limits:
Humans
Language:
English
Journal:
Stem Cell Reports
Year:
2021
Document Type:
Article
Affiliation country:
J.stemcr.2021.02.005
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